Reduced Number of Hypocretin Neurons in Human Narcolepsy

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Reduced Number of Hypocretin Neurons in Human Narcolepsy Thomas C. Thannickal, Robert Y. Moore, Robert Nienhuis, Lalini Ramanathan, Seema Gulyani, Michael Aldrich, Marsha Cornford, Jerome M. Siegel  Neuron  Volume 27, Issue 3, Pages 469-474 (September 2000) DOI: 10.1016/S0896-6273(00)00058-1

Figure 1 Distribution of Hypocretin-Labeled Somas in Normal and Narcoleptic Subjects Normal is subject CG, and narcoleptic is subject NA. Cell counts are listed below each section. On average, the narcoleptics had only 7% of the Hcrt cells seen in normals. Neuron 2000 27, 469-474DOI: (10.1016/S0896-6273(00)00058-1)

Figure 2 Distribution of Cells in Perifornical and Dorsomedial Hypothalamic Regions of Normal and Narcoleptic Humans Plotted in Figure 1 All cells in figure are from the levels indicated in (A) and (B). (C and D) Low power photomicrographs calibration Cal. = 100 μm covering regions outlined in gray at the top shows many Hcrt somas and axons in the normal and few in the narcoleptic (arrows in narcoleptic indicate Hcrt somas verified as immunolabeled at higher magnification). Higher power photomicrographs Cal. = 25μm show Hcrt cells and axons in normal (E and G) and narcoleptic (F and H) subjects. Note the reduced density of axonal staining in the background of the narcoleptic as compared to that seen in the normal. Neuron 2000 27, 469-474DOI: (10.1016/S0896-6273(00)00058-1)

Figure 3 The Number of Hcrt Cells Is Decreased in Narcoleptics Neuron 2000 27, 469-474DOI: (10.1016/S0896-6273(00)00058-1)

Figure 4 Melanin-Concentrating Hormone Neurons in Normal and Narcoleptic Subjects Normal is subject CK, and narcoleptic is subject NA. Narcoleptics have normal numbers of MCH neurons despite the loss of 93% of Hcrt cells in the same region. Cal. = 250 μm. Neuron 2000 27, 469-474DOI: (10.1016/S0896-6273(00)00058-1)

Figure 5 Glial Fibrillary Acidic Protein–Labeled Astrocytes in the Periventricular/Perifornical Region of a Normal and Narcoleptic Brain Low power photomicrograph is at the top, and a higher magnification of area marked with plus signs is at the bottom. Elevated GFAP staining in the hypothalamus of narcoleptics is consistent with a degenerative cause of cell loss. TopCal. = 500 μm; bottomCal. = 50 μm. Neuron 2000 27, 469-474DOI: (10.1016/S0896-6273(00)00058-1)

Figure 6 Pattern of Gliosis in the Hypothalamus and Thalamus of Narcoleptics and Controls The number of GFAP labeled astrocytes is significantly increased in the hypothalamus of narcoleptics, the region containing Hcrt cells, but not in the thalamus. Neuron 2000 27, 469-474DOI: (10.1016/S0896-6273(00)00058-1)